Measles virus was first isolated in cell culture in 1954 from David Edmonston. The Edmonston strain of measles virus became the progenitor for many live-attenuated measles vaccine strains which include Moraten, see Hilleman et al., JAMA 206: 587-90 (1968), currently the only licensed measles vaccine strain in the United States. Aggressive vaccination programs instituted in the mid-1960's resulted in a precipitous drop in reported measles cases from near 700,000 in 1965 to only 1500 in 1983.
Since 1989 dramatic increases in both the numbers and severity of measles cases were reported. In 1989, greater than 17,000 cases of measles and 43 associated deaths were reported in the United States. Nearly 100 fatalities from measles-associated illnesses and greater than 27,000 cases of measles were reported in 1990. Approximately half of the measles cases were in unvaccinated preschool populations, whereas the remaining 50% were in previously vaccinated populations. Outbreaks have continued to occur into 1991, at approximately the rate observed in 1989.
The resurgence of measles is not understood causally, but may be attributed to a failure to vaccinate key inner city populations and to a low but significant rate of primary vaccine failure to raise immunity (estimated at 3-5%). Secondary vaccine failure, which occurs when a person's post-vaccination titre of antibodies drops to a non-protective level after an period of time passes, also is a suspected cause.
The measles resurgence is reflected in a rising epidemic of measles infections among young, previously-immunized adults, in particular persons who are immunocompromised. To account for this development in measles epidemiology, it is postulated that transmission of virus is occurring from vaccinated individuals who harbor subclinical measles infections, or, alternatively, that infection arises from the live-attenuated vaccine itself.
The effort to curb the measles resurgence has focused on the role played by measles virus structural proteins in inducing immunity in a vaccinated mammal. The measles virus, like many members of the paramyxovirus family, contains six major structural proteins: the matrix protein, hemagglutinin, the fusion protein, large protein, phosphoprotein and nucleocapsid protein. Of these, the envelope glycoproteins, hemagglutinin and fusion, have been shown to be responsible for induction of measles virus-neutralizing antibodies. See Varsanyi et al., J. Gen. Virol. 65: 365 (1984), Giraudon et al., Virology 144: 46 (1985), and Drillien et al., Proc. Nat'l. Acad. Sci. USA 85: 1252-56 (1988).
The matrix gene has been the focus of much of the previous genetic research, due to evidence that this gene may play a role in the establishment of persistent infections. Recently, nucleotide sequences encoding matrix protein from the two wild-type measles virus isolates (JM and CM) were compared and found to be distinct from vaccine strain sequence. See Baczko et al., J. Gen. Virol. 72 (Pt 9): 2279-82 (1991). In comparing measles fusion protein with fusion proteins of other paramyxoviruses, the Halle strain of measles was found to contain no amino acid differences from that of the Edmonston vaccine strain fusion protein. See Buckland et al., J. Gen. Virol. 68 (6): 1695-1704 (1987).
Research efforts thus far have mostly been directed towards understanding measles genetics using the more readily available vaccine strains, as opposed to wild-type measles viruses, which are difficult to isolate from an infection. Additionally, because measles virus infections have only recently begun to resurge, no one has thus far attempted to study variations in measles glycoproteins of circulating wild-type virus populations, as compared to a vaccine strain.
Thus, to date, there has been no detection of variations from vaccine strain measles virus glycoproteins which are conserved amongst wild-type strains. Further, no effective vaccine has been proposed to offer protective resistance against recently-emerging wild-type strains.
There is also a notable absence of diagnostic technologies which specifically recognize wild-type viral strains from a vaccine strain. As a consequence, the causal agent of an infection is not readily distinguishable between wild-type or vaccine strains, which in turn makes etiological and epidemiological studies difficult. It is important to distinguish whether a vaccine or exposure to wild-type measles caused an infection, for example, where measles infection arises in an immunocompromised individual previously immunized with measles vaccine.